Bone marrow transplantation (BMT) is a well-established approach to the treatment of malignant and non-malignant hematopoietic diseases, although it is considered as a last resort. Even when using matched donors, many patients develop graft-versus-host disease (GVHD), which, when not fatal, can progress to a chronic, lifelong condition. Symptoms of GVHD can involve a number of tissues and organs, including the skin, hair, lungs, liver, and the gastrointestinal tract. Current treatments include immune suppressive agents and steroids, although these regimens do not work for all patients. Thus, effective, non-toxic, long-term treatment for chronic GVHD is imperative. The preimplantation factor (PIF) is an evolutionarily-conserved peptide that accompanies and supports viable embryo development, regulating inflammation, immunity and transplant acceptance. PIF has been shown to regulate several pro-inflammatory genes and proteins, to block activated T-cell proliferation, and to reduce oxidative stress. Synthetic PIF (sPIF) activity in the GVHD context was assessed following BMT. Short-term, low-dose administration of sPIF in preclinical models was shown to promote and sustain engraftment of donor bone marrow cells, prevent the development of GVHD, preserve the beneficial graft versus leukemia effect, and significantly reduce overall mortality. PIF treatment led to protection against dermatitis, hepatitis, and colon ulceration, the three classic hallmarks of GVHD. PIF treatment reduced mortality following allogeneic BMT from an unrelated donor, and promoted long-term cellular engraftment in syngeneic transplant from a genetically identical donor. These findings suggest that PIF could be useful against the range of adverse effects that develop acutely and chronically after BMT, which may make the overall procedure more feasible, rather than a last resort. The team is collaborating on the completion of the following studies: - Synthesis of Good Manufacturing Practice (GMP) material - Investigational New Drug (IND)-directed toxicology